Granulocyte Colony-Stimulating Factor Enhances the Angiogenetic Effect of Indirect Bypass Surgery for Chronic Cerebral Hypoperfusion in a Rat Model

Abstract

Granulocyte colony-stimulating factor (G-CSF) mobilizes hematopoietic bone marrow cells into systemic circulation and has been used clinically to treat chemotherapy-induced neutropenia. Recently, G-CSF was shown to have neuroprotective and angiogenetic effects in acute cerebral infarction. To evaluate the effects of G-CSF for angiogenesis after indirect bypass surgery. : Chronic cerebral hypoperfusions were induced in male Wistar rats by permanent bilateral internal carotid artery occlusion (BICAO). After BICAO, unilateral indirect bypass and encephalogaleosynangiosis (EGS) were performed, and human recombinant G-CSF (10 μg/kg) or saline was injected intramuscularly for 5 consecutive days. We measured regional cerebral blood flow (rCBF) by laser Doppler flowmetry and performed immunohistochemical analysis 21 days after BICAO. BICAO decreased rCBF to 62.52% ± 5.8% of control (P < .01). The rCBF increased significantly 21 days after BICAO in all treatment groups (n = 10; P < .05) except the G-E- group. The rCBF increase observed in the G+E+ group was significantly higher than that observed in other groups. Both G-CSF and EGS treatments significantly increased the number of small vessels (P < .01), and G-CSF and EGS showed additive effect in increasing the number of small vessels. Combined use of G-CSF and indirect bypass surgery induces an increase in rCBF and angiogenesis under conditions of cerebral chronic hypoperfusion. This is the first report to demonstrate that G-CSF can enhance angiogenesis induced by indirect bypass surgery, and that this combined therapy is a safe and easy method of treatment.